There are countless questions when it comes to medical cannabis and colorectal cancer: How can it help? How do you get it? Are there drug interactions with chemo? What are the side effects? Is it legal where I live?

1. Clearing the Air: The Role of Medical
Marijuana in Cancer Patients

2. TODAY’S WEBINAR
 SPEAKER(S)
 Lisa M. Holle, PharmD, BCOP, FHOPA
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3. RESOURCE
S
TABOO-TY PODCAST MINI MAGAZINES CLINICAL TRIAL FINDER

4. FIGHTCOLORECTALCANCER
DISCLAIMER
The information and services provided
by Fight Colorectal Cancer are for
general informational purposes only.
The information and services are not
intended to be substitutes for
professional medical advice,
diagnoses or treatment.
If you are ill, or suspect that you are
ill, see a doctor immediately. In an
emergency, call 911 or go to the
nearest emergency room.
Fight Colorectal Cancer never
recommends or endorses any specific
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any condition.

5. LisaM.Holle,PharmD,BCOP,
FHOPA
Bio: Dr. Holle is an Associate Clinical Professor of Pharmacy Practice
in the Department of Pharmacy Practice at the UConn School of
Medicine. Her current research interests include those which
evaluate the impact of oncology pharmacy practice services on
patient care, adherence to and patient education/understanding of
appropriate use of orally administered oncology medications.
Ongoing and future projects will focus on the patient-related
outcomes of oncology pharmacy practice care within a team-based
approach and pharmacist-led education and cancer risk-
assessment/screening in the community pharmacy setting. Past
research has included the impact of drug shortages on cancer care;
collaborative cancer therapy and supportive care clinical trials in the
hematopoietic stem cell and oncology setting; and quality
improvement research related to oncology medication safety.

6. Clearing the Air:
The Role of Medical Marijuana in
Cancer Patients
Lisa M. Holle, PharmD, BCOP, FHOPA
Associate Clinical Professor, School of Pharmacy
Associate Professor, School of Medicine
lisa.holle@uconn.edu

7. What is Medical Marijuana?
• Cannabis – produced from Cannabis sativa/indica/ruderalis
– Marijuana – flower/leaves
– Hashish – blocks of resin
• Cannabinoids – exhibit drug-like effects
– Endogenous cannabinoids
– Phytocannabinoids – produced by Cannabis sativa and
indica species
– Synthetic cannabinoids
• Medical marijuana – use of phytocannabinoids or synthetic
cannabinoids
Parmer J, et al. Res Soc Admin Pharm. 2015. [published ahead of print]

8. Medical Marijuana History
Western
Medicine
Marihuana
Tax Act
Narcotic
Schedule
I
Compass-
ionate
Use
Synthetic
drugs
Medical
Use
CBD Oral
Solution
FDA
approved
CBD, cannabidiol.
National Cancer Institute. Available at: http://www.cancer.gov/about-
cancer/treatment/cam/hp/cannabis-pdq#section/_5 . Accessed March 24, 2019.
1840s 1937 1951 1970 1971-1990 1986 1980s-90s 2018

9. Medical Marijuana. ProCon.org. Available at:
https://medicalmarijuana.procon.org/view.resource.php?resourceID=000881. Accessed
March 24, 2019.

10. Differences in State Medical
Marijuana Programs
• Laws very greatly
• Approved conditions
• Possession amounts/cultivation allowed
• Registration processes
• Allow dispensaries (does not allow dispensaries OR, NE,
MI, HI)
• Pharmacist oversight of dispensaries (AK, CT, MN, NY,
OK, PA); marijuana pharmacies (LA, UT)
• Specify conditions in which it can be used
• Recognize patients from other status (AZ, AR, ME, MI,
NE, NH, OK, RI)
Medical Marijuana. ProConorg. Available at:
https://medicalmarijuana.procon.org/view.resource.php?resourceID=000881. Accessed 5 Jan 2019.

11. How Medical Marijuana Works
In the Body

12. What Are The Different Types
Recreated from Turgeman I, et al. Expert Opin Invest Drugs. 2018 (in press): DOI:
10.1080/13543784.2019.1561859.
Cannabis Plant
(sativa, indica, ruderalis)
Phytocannabinoid
THC
CBD
Cannabinol
Tetrahydro-
cannabivarin
Cannabigerol
Terpenoid
Limonen
Terinolen
Pinene
Flavonoid
Canna-
flavin A
Orientin
Quercetin
• Anandamide
• 2-arachidononyl-
gylcerol
Endogenous
Cannabinoid
System
• Classical
•Nabilone
•Dronabinol
• Nonclassical
•JWH-018
•Methanadmide
•AM4030
Synthetic
Cannabinoids

13. What Effects Does it Have?
Recreated from Turgeman I, et al. Expert Opin Invest Drugs. 2018 (in press): DOI:
10.1080/13543784.2019.1561859.
• Cannabinoids in
marijuana
– Delta-9-
tetrahydrocannabidiol
(THC)
– Cannabidiol (CBD)

14. Biologic Effects
Guzman M. N Rev Cancer. 2003;3:745-755.
CB1 – central and peripheral neurons; CB2 – immune system.

15. How You Can Take Medical Marijuana
Bowels DW, et al. Crit Rev Oncol/Hematol. 2012;83:1-10; Kramer JL. CA Cancer J
Clin. 2015;65:109-122.
• Inhalation
• Oral
• Rectal
• Sublingual
• Transdermal
• Ophthalmic
• Intrathecal
• Intravenous

16. What About CBD Oil?
• 2014 United States
Farm Act
– Classified industrial
hemp as containing <
0.3% THC
– Allowed to be sold in all
50 states
– Other ingredients?
– Regulated?

17. FDA Approved Synthetic Products
• Dronabinol (Marinol®)
– Synthetic THC
– CINV failing other treatments
– Weight loss and anorexia with AIDS
– Schedule III
• Nabilone (Cesamet®)
– Synthetic THC-mimetic
– CINV failing other treatments
– Schedule II
CINV, chemotherapy-induced nausea and vomiting; FDA, US Food and Drug
Administration.
Bowels DW, et al. Crit Rev Oncol/Hematol. 2012;83:1-10; Kramer JL. CA Cancer J Clin.
2015;65:109-122.

18. Approved Oral Products
Nabiximols (Sativex®)
• THC + CBD extract
• Multiple sclerosis and
cancer pain
• Not available in US
Cannabidiol (Epidiolex®)
• Plant-derived oral CBD
solution
• June 2018: FDA approved
• Treatment of seizures
associated with Lenox-
Gastaut syndrome or
Dravet syndrome in
patients > 2 years
• September 2018 – DEA
Schedule 5
• CT: Schedule 2
FDA, US Food and Drug Administration Approved. Drug Enforcement Agency.
Available at: https://www.dea.gov/press-releases/2018/09/27/fda-approved-drug-
epidiolex-placed-schedule-v-controlled-substance-act. Accessed March 24, 2019.

19. How Your Body Absorbs It
Dosage Form Absorption
Peak
Level
Factors Impacting
Absorption Bioavailability
Inhalation Quick fast,
rapid
delivery to
brain
22 min Depth of inhalation,
frequency of puffs,
breath hold
Varies: 2-56%
Heavy: 23-27%
Occasional:
10-14%
Oral Slow 1-2 h;
up to 8 h
Degradation of drug in
stomach and first-pass
10-20%
Oral-mucosal/
buccal
Fast 30 min High first-pass
metabolism
10-20%
Rectal Fast 15 min Low first-pass
metabolism
20-40%
Transcutaneous Slow 2 hr; up
to 48 h
Transport across skin
layers; no first-pass
metabolism
10%
Oberbarnscheidt T, et al. J Addict Res Ther. 2017;S11:012.
Crosses placenta and into breast milk.

20. How Your Body Digests It
• Metabolism
– Liver metabolism
– Other metabolism: brain, intestine, lung
• Drug Interactions
– Medications that cause drowsiness/dizziness
– Many potential interactions
CBD, cannabidiol; CYP450, cytochrome P450; THC, delta-9-tetrahydrocannabinoid.
MacCallum CA, et al. Eur J Inter Med. 2018;49:12-19; Epidiolex [package insert]. Carlsbad, CA:
Greenwich Biosciences, Inc: 2018.

21. What’s the Evidence?

23. Cancer Treatment
• Multiple pathways explored in preclinical models
• Phase I refractory glioblastoma
• Case report: astrocytomas
• Case report: acute lymphoblastic leukemia
• In progress
– Phase II placebo-controlled THC:CBD preparation +
temozolomide in glioblastoma – safe; survival advantage
– Phase II nabiximols + temozolomide in glioblastoma
– Two phase I dexananibol – advanced solid tumors and
brain cancers
– Retrospective review of immunotherapy + cannabis
effects
CBD, cannabidiol; THC, delta-9-tetrahydrocannabinoid.
Turgeman I, et al. Expert Opin Invest Drugs. 2018 (in press): DOI:
10.1080/13543784.2019.156185.

24. Immunotherapy and Cannabis
• Retrospective review of nivolumab-treated patients at
Ramban Health Care Campus; Haifa, Israel
• N=140 patients (nivolumab, 89; nivolumab + cannabis,
51)
• Advanced melanoma, non-small cell lung cancer, renal
cell carcinoma
• Results
– Cannabis only factor which reduced reduced response rate
(nivolumab, 37%; combination, 15.9%
– Cannabis did not affect overall or progression-free survival
Taha T, et al. Ann Oncol. 2017;28(5):1545PD.

25. Cancer Symptoms

26. Nausea and Vomiting
• 30 studies published
– Smoked THC
– Synthetic cannabinoids
– Nabiximols
• Meta-analysis found compared with placebo
– Significantly more effective for nausea and
vomiting
• Not evaluated with current antiemetic
regimens

27. Cancer-Associated Pain
Study Design Patients Therapy Results
Noyes
1975
RCT/DB/PC Cancer
pain
N=10
Dronabinol
5mg, 10mg
15mg and
20mg vs
placebo
15 and 20 mg - substantial analgesic effects;
antiemesis and appetite stimulation; 20 mg = 120
mg codeine
Johnson
2010
RCT/DB/PC Cancer
pain
N=177
Nabiximols vs
THC 2.7 mg
oromucosal
spray vs
placebo
• Significantly improved mean pain score; > 30%
reduction in pain from baseline score for
THC/CBD product
• No change for THC product
• No change in mean opioid dose or
breakthrough doses
Portenoy
2012
RCT/DB/PC Cancer
pain
N=360
Nabiximols
(low, medium,
high dose) vs
placebo
• Better pain control and sleep disruption with
low dose compared with placebo
• Adverse events dose related
Lynch
2014
RCT/PC CIN
N=16
Nabiximols vs
placebo
• No statistical difference on numeric pain rating
• 5 responders decreased 2.6 on 11-pt scale
CBD, cannabidiol; DB, double-blind; PC, placebo-controlled; RCT, randomized controlled trial; THC,
delta-9-tetrahydrocannabinoid. Noyes R, et al. Clin Pharmacol Therp. 1975;18;84-89; Noyes R, et
al. J Clin Pharmacol. 1975;15:139-143; Johnson JR, et al. J Symptom Manage. 2010;39:167-178;
Portenoy RK, et al. J Pain. 2012;13:438-449; Lynch ME, et al. J Symptom Manage. 2014;47:166-
173.

28. Anorexia/Weight Gain
• Appetite increase: 49%
• Weight gain: 3%Dronabinol 2.5 mg
po BID + placebo
• Appetite increase: 75%
(P=.0001)
• Weight gain: 11% (P=.02)
• Improved QOL and toxicity
Megestrol 800 mg
po daily + placebo
• Appetite increase: 66% (P=.17)
• Weight gain: 8% (P=.43)
Dronabinol 2.5 mg
BID + Megestrol
800 mg po daily
Randomized,
double-blind,
parallel group
N=469
Advanced
cancer
Weight loss
QOL, quality of life.
Jatoi A, et al. J Clin Oncol. 2002;20:567-573; Strasser F, et al . J Clin Oncol. 2006;24:3394-3400.

29. Anorexia & Cachexia
Increased appetite:
• Cannabis extract: 73%
• THC: 58%
• Placebo: 69%
No significant differences in:
• Appetite
• QOL
• Toxicity
Cannabis extract
(THC 2.5 mg
CBD: 1 mg)
(n=66)
THC 2.5 mg
(n=65)
Adult patients
Advanced cancer
Cancer-related
anorexia and/or
cachexia
ECOG PS < 2
R
A
N
D
O
M
I
Z
E
D
2:2:1
ECOG, Eastern Cooperative Oncology Group; CBD, cannabidiol; THC, delta-9-
tetrahydrocannabinoid.
Strasser F, et al. J Clin Oncol. 2006;24:3394-3400.
Placebo
(n=33)

30. Cannabinoids for Insomnia
• Meta-analysis of 19 placebo-controlled studies
– Cannabis-products evaluated for other indications
and evaluated sleep
– Nabiximols: 13 studies
– THC/CBD capsules: 2 studies
– Smoked THC: 2 studies
– Dronabinol: 1 study
– Nabilone: 1 study
• Greater average improvement in
– Sleep quality
– Sleep disturbance
CBD, cannabidiol; CI, confidence interval; THC, delta-9-tetrahydrocannabinoid.
Whiting PF, et al. JAMA. 2015;313:2456-2473.

31. Depression and Anxiety
• No studies specific in cancer patients
• Meta-analyses of indications
– No well designed trials evaluating depression
– Depression as an outcome: no difference found
compared with placebo
– Positive for individuals with social anxiety and
anxiety in chronic pain patients
Whiting PF, et al. JAMA. 2015;313:2456-2473.

32. Adverse Effects of
Cannabis-Based Medications
Most Common Common Rare
Drowsiness/fatigue Euphoria Orthostatic hypotension
Dizziness Blurred vision Toxic psychosis/paranoia
Dry mouth Headache Depression
Cough/phlegm/ bronchitis
(smoking only)
Ataxia/dyscoordination
Anxiety Tachycardia (after
titration)
Nausea Hyperemesis
Cognitive effects Diarrhea
MacCallum CA, et al. Eur J Inter Med. 2018;49:12-19.
• Schizophrenia/bipolar disorder, long-term cognitive dysfunction

33. COMPASS Study
•Nonserious AEs: 88.4% vs 85.2%
•Cannabis: nervous system, GI, respiratory
•Serious adverse effects: 13% (cannabis)
vs 19%
•Deaths: 0% vs 1%
Primary objective
Assess risk of adverse
events
•No significant change in pulmonary
function tests
•No difference in neurocognition at 1
year
•No changes in liver, renal, or endocrine
labs
•Significant reduction in average pain
intensity at 1 yr: change, 0.92 vs 0.18
•QOL; 2.36 points greater with cannabis
Secondary objective
Pulmonary function
Neurocognitive
function
Other safety
Effect on pain and QOL
AE; adverse events; QOL, quality of life; THC; delta-9-tetrahydrocannabinoid.
Ware MA, et al. J Pain. 2015;16:1233-1241.
Prospective,
cohort study
Jan 2004-April
2008
Adults chronic
non-cancer
pain using
cannabis
(12.5% THC),
any delivery
system vs
control
population

34. Cannabinoid Hyperemesis Syndrome
• Recurrent paroxysmal episodes of nausea/vomiting in chronic users
• Mitigated by frequent hot bathing/showering
• Complications: acute renal failure, electrolyte depletion,
pnuemomediastinum
• Acute treatment
– Replace fluids
– Medications
• Antiemetic
• Anxiolytics
• Antiphsycotics
• Capsaicin topical
– Hot showers
• Long-term treatment
– Stop cannabis use
N/V nausea and vomiting; 5HT3; 5-hydroxytryptamin or serotonin.
Richards JR, et al. Pharmacother. 2017;37:725-734; Health Canada.
https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-
medication/cannabis/information-medical-practitioners/information-health-care-professionals-
cannabis-cannabinoids-eng.pdf. Accessed March 24, 2019.

35. Contraindications
• Allergy to any cannabinoid
• Past history of psychotic disorder
• Active or unstable cardiovascular disease
Caution
• Pregnant or nursing women
• Potential for dependence/abuse
• Driving
Canadian Consortium for the Investigation of Cannabinoids. Available at www.ccic.net.
Accessed March 24, 2019.

36. Now That You Have the Evidence….

37. What are Legal Implications?
State laws allow
US Dept Justice stance
Patient benefits
Schedule I
Institution stance
Medical association stance
Hill. JAMA. 2015;313:2474-2480.

38. When to Use?
• Qualifying condition
• Multiple failed trials of first- and second-line
pharmacotherapies
• Failed trial of FDA approved cannabinoid
• No active substance, psychiatric, unstable
mood or anxiety disorder
Hill. JAMA. 2015;313:2474-2480.

39. State Medical Marijuana Programs
• Provider certifies patient
with qualifying condition
• Patient registers, some
states allow caregivers
• Go to dispensary to
purchase product
Department of Consumer Protection Medical Marijuana Program. Available at:
https://portal.ct.gov/DCP/Medical-Marijuana-Program/Medical-Marijuana-
Statistics. Accessed March 24, 2019.

40. CT Qualifying Conditions - Adults
Amyotrophic lateral sclerosis HIV/AIDS Post herpetic neuralgia
Cachexia Intractable HA syndrome Psoriasis (severe)
Cancer Multiple sclerosis Psoriatic arthritis
Cerebral palsy Muscular dystrophy Rheumatoid arthritis severe
Complex regional pain
syndrome
Hydrocephalus with
intractable HA
Terminal illness requiring end-
of-life care
Crohn’s disease Neuropathic facial pain Sickle cell disease
Cystic fibrosis Osteogenesis imperfecta Ulcerative colitis
Epilepsy Parkinson disease Uncontrolled intractable
seizure disorder
Glaucoma PTSD Wasting syndrome
Damage to spinal cord with
intractable spasticity or
irreversible cord injury
Fibromyalgia
(spasticity/neuropathic
pain)
Post laminectomy syndrome
with chronic radiculopathy
Department of Consumer Protection Medical Marijuana Program. Available at:
https://portal.ct.gov/DCP/Medical-Marijuana-Program/Qualification-
Requirements. Accessed March 24, 2019.

41. CT Qualifying Conditions - Children
Cerebral palsy
Cystic fibrosis
Irreversible spinal cord injury with objective neurological indication of intractable
spasticity
Muscular dystrophy
Osteogenesis imperfecta
Severe epilepsy
Terminal illness requiring end-of-life care
Uncontrolled intractable seizure disorder
Department of Consumer Protection Medical Marijuana Program. Available at:
https://portal.ct.gov/DCP/Medical-Marijuana-Program/Qualification-
Requirements. Accessed March 24, 2019

42. Dispensaries in CT
• CT licensed pharmacists
• Similar restrictions/requirements as pharmacy
• Security system
• Qualified patients and
caregivers allowed in facility
• No compounding
• Review PMP
Department of Consumer Protection Medical Marijuana Program. Available at:
https://portal.ct.gov/DCP/Medical-Marijuana-Program/Dispensary-Facility.
Accessed March 24, 2019.

43. Dispensary Pharmacist’s Role
• Complete an initial patient
assessment
– What symptoms require relief?
– Naïve vs experienced user
– Patient’s lifestyle
• Help patient select product
– Strain, dosage form, delivery device
– Variations on time to effect, adverse
effects
• Equip patient with tools to self-
assess efficacy of product
• Report any adverse events that may
occur

44. Medical Marijuana in Hospitals
• Pharmacologic implications
• Legal challenges
• Federal compliance for funding/licensure
• Acquisition of product
• Other considerations
– No smoking policy
– Training
– Monitoring/outcomes
• Typical policies
– Not allowed for inpatients

45. How Your Healthcare Provider Should
Monitor Your Use
• Changes in
– Medical condition/symptoms
– Physical or psychosocial function
– Medication list
• Efficacy of treatment
• Adverse effects
• Liver function tests?
• Safety of use (possible diversion, driving/equipment
use)
• Goals of treatment
• Progress towards goals
Medical Board of California. Available at:
https://www.mbc.ca.gov/Publications/guidelines_cannabis_recommendation.pdf.
Accessed 6 January 2019; Epidiolex [package insert]. Carlsbad, CA: Greenwich Biosciences,
Inc: 2018..

46. What You Need To Know
• Registration process
• Variability of quality and concentration of cannabis
• Dosing and dosage forms (start low and go slow)
• Potential risks of cannabis
– Adverse effects
– Pregnancy/lactation
– Drug interactions
• Financing, travel
• Safeguards to prevent diversion
• Symptom inventory chart
Medical Board of California. Available at:
https://www.mbc.ca.gov/Publications/guidelines_cannabis_recommendation.pdf.
Accessed 6 January 2019.

47. Summary
• THC and CBD are primarily responsible for medicinal
effects
• Limited data supports medical marijuana use in cancer
and associated symptoms; yet many patients have benefit.
This may be due to the lack of well designed studies
• Most side effects are transient and can be treated by
adjusting doses
• Patient certification process can be facilitated by
dispensary staff

48. Resources
• Centers for Disease Control:
https://www.cdc.gov/marijuana/index.htm
• NIH: https://nccih.nih.gov/health/marijuana
• Health Canada:
https://www.canada.ca/en/health-
canada/topics/cannabis-for-medical-
purposes.html

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